Pharmakokinetik und Pharmakodynamik der in der assistierten Reproduktion verwendeten Gestagene

Zusammenfassung Progesteron wird in der mittleren bis späten Lutealphase pulsatil aus dem Corpus luteum sezerniert, wobei die Serumspiegel innerhalb weniger Stunden bis zum 8‑fachen Wert fluktuieren. Bei einer In-vitro-Fertilisations-Behandlung kann es, bedingt durch die ovarielle Hyperstimulation in Kombination mit einer hypophysären Down-Regulation, zu einem Lutealphasendefekt kommen. Aus diesem Grund wird die Lutealphase im Rahmen der assistierten Reproduktion meist mit Progesteron oder Dydrogesteron unterstützt, wobei Dydrogesteron stets oral, Progesteron jedoch meist parenteral (vaginal, subkutan oder intramuskulär) angewendet wird. Bei einer oralen Progesteronbehandlung entstehen durch extensive Metabolisierung mehr als 30 Metaboliten, die zum Teil erhebliche zentrale (sedierende) Wirkungen entfalten. Einige dieser Metaboliten können bei der Progesteronbestimmung mit einem Radioimmunassay durch Kreuzreaktionen falsch-hohe Progesteronwerte simulieren. Bei der parenteralen Behandlung besteht diese Gefahr aufgrund nur geringer Metabolisierung nicht. Die Retrostruktur von Dydrogesteron lässt die Bildung nur weniger Metaboliten zu, die zudem keine zentralen Effekte aufweisen. Die höchsten Progesteronkonzentrationen werden im Serum nach intramuskulärer und im Endometrium nach vaginaler Behandlung erreicht; ursächlich für Letzteres ist vermutlich ein uteriner First-pass-Effekt. Die transdermale Progesteronapplikation in Form einer Creme bewirkt nur einen sehr geringen Anstieg des Progesteronspiegels. Zur Kontrolle einer Progesterontherapie sind Bestimmungen im Speichel aufgrund stark schwankender Progesteronkonzentrationen nicht geeignet. Abstract Progesterone is secreted from the corpus luteum in a pulsatile manner. During the mid to late luteal phase the plasma concentrations may rapidly fluctuate up to eight-fold within a few hours. In vitro fertilization (IVF) treatment can promote the occurrence of luteal phase insufficiency due to ovarian hyperstimulation combined with pituitary down-regulation. Therefore, progesterone or dydrogesterone (DYD) is routinely administered in IVF treatment in order to improve embryo implantation during the luteal phase. In contrast to DYD, which is always orally used, progesterone is predominantly administered parenterally (vaginally, s.c. or i.m.) in assisted reproductive technology cycles. Oral administration of progesterone causes extensive metabolism resulting in the formation of more than 30 metabolites, some of which may cause anaesthetic/sedative effects. The use of a direct radioimmunoassay (RIA) without prior separation of progesterone from its metabolites may simulate falsely high serum concentrations of progesterone owing to cross-reaction of some metabolites with the specific antiserum of the RIA. This effect is not observed after parenteral treatment with progesterone due to minimal metabolism. The rigid retrostructure of DYD allows only the formation of a few metabolites. After vaginal administration of progesterone, the endometrial and myometrial progesterone concentrations are markedly higher than those after i.m. injection of an oily suspension of progesterone. This suggests a direct diffusion and deposition of progesterone in the uterus (uterine first-pass effect). The systemic absorption of transdermal progesterone is low. Progesterone measurements in saliva are not recommended for monitoring progesterone treatment due to large variations of progesterone levels in saliva. Similar content being viewed by others Literatur Griesinger G, Tournaye H, Macklon N et al (2019) Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. 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Maturitas 13:313–317 Gelbe Liste (2020) Fachinformation „Prolutex 25 mg Injektionslösung“ Sator M, Radicioni M, Cometti B et al (2013) Pharmacokinetics and safety profile of a novel progesterone aqueous formulation administered by the s.c. route. Gynecol Endocrinol 29:205–208 Author information Authors and Affiliations Corresponding authors Ethics declarations Interessenkonflikt H. Kuhl und I. Wiegratz geben an, dass kein Interessenkonflikt besteht. Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. Additional information Redaktion G. Griesinger, Lübeck Rights and permissions About this article Cite this article Kuhl, H., Wiegratz, I. Pharmakokinetik und Pharmakodynamik der in der assistierten Reproduktion verwendeten Gestagene. Gynäkologische Endokrinologie 19, 105–117 (2021). https://doi.org/10.1007/s10304-020-00372-5 Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10304-020-00372-5